Arminja N. Kettenbach, PhD
Professor of Biochemistry and Cell Biology
Biochemistry and Cell Biology
Molecular and Cellular Biology Graduate Programs
Norris Cotton Cancer Center
Program in Experimental and Molecular Medicine
One Medical Center Drive
HB - 7937
Lebanon NH 03756
Office: Rubin 763
More than three-quarters of all proteins are phosphorylated at one or more sites in human cells. A ‘tug of war’ between kinases and phosphatases establishes the phosphorylation states of proteins to control their function. To understand how protein phosphorylation regulates complex biological processes, we must investigate both forward and reverse reactions, connecting kinases and phosphatases on their shared substrates. Although there has been great progress in deciphering signaling by kinases, much less is known about phosphatases.
Research in my laboratory focuses on uncovering previously unrecognized roles of phosphatases in cellular signaling networks in normal tissues and in cancer. We establish specific phosphatase-substrate relationships, identify opposing kinases, and determine regulatory inputs. While previous studies have mainly concentrated on one enzyme at a time [3-5], my research program looks at cellular networks as a whole. My laboratory is uniquely positioned for this work because we combine systematic quantitative measurements of the proteome and phosphoproteome with reconstitution of minimal signaling units in vitro, so as to specify phosphatase behavior precisely.
Activity-based profiling of protein phosphatases in cancer (The V Foundation for Cancer Research)
Mechanisms of phosphorylation signaling by phosphoprotein phosphatases (R35 GM119455 NIH/NIGMS)
Proteomic approaches to target the PP6-mTORC2 pathway in glioblastoma (P20 GM113132 NIH/NIGMS)
Geisel – BIOC 110: Biochemical and genetic basis of medicine
Role: Discussion group leader
MCB – BIOC 101: Molecular information in biological systems.
Dr. Arminja Kettenbach is currently a Professor of Biochemistry and Cell Biology at the Geisel School of Medicine at Dartmouth College. Arminja earned her Master degree (Diplom) in Biochemistry at the Eberhard-Karls University in Tuebingen, Germany, in 2002. For her PhD, she joined the laboratory of Dr. Frank McKeon in the Department of Cell Biology at Harvard Medical School, Boston, in 2003. Her thesis work focused on mechanisms of cell division and cell differentiation. It was there that Arminja was exposed first to mass spectrometry-based proteomics and decided to further explore this field for her post-doctoral studies. In 2007, she joined the laboratory of Dr. Scott Gerber in the Department of Genetics at the Geisel School of Medicine at Dartmouth College where she pioneered quantitative phosphoproteomics approaches to study cell signaling. As an independent investigator, Dr. Kettenbach is focused on understanding signaling by phosphoprotein phosphatases and their cellular networks in triple-negative breast cancer (TNBC) by combining technology development, studies of cell culture models and human primary tumors.
Petrone A, Adamo ME, Cheng C, Kettenbach AN. Identification of Candidate Cyclin-dependent kinase 1 (Cdk1) Substrates in Mitosis by Quantitative Phosphoproteomics. Molecular & cellular proteomics : MCP. 2016; 15(7):2448-61. (view details in PubMed)
Rusin SF, Schlosser KA, Adamo ME, Kettenbach AN. Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells. Science signaling. 2015; 8(398):rs12 (view details in PubMed)
Kettenbach AN, Deng L, Wu Y, Baldissard S, Adamo ME, Gerber SA, Moseley JB. Quantitative phosphoproteomics reveals pathways for coordination of cell growth and division by the conserved fission yeast kinase pom1. Molecular & cellular proteomics : MCP. 2015; 14(5):1275-87. (view details in PubMed)
Kettenbach AN, Wang T, Faherty BK, Madden DR, Knapp S, Bailey-Kellogg C, Gerber SA. Rapid determination of multiple linear kinase substrate motifs by mass spectrometry. Chem Biol. 2012 May 25;19(5):608-18. (view details in PubMed)
Kettenbach AN, Gerber SA. Rapid and reproducible single-stage phosphopeptide enrichment of complex peptide mixtures: application to general and phosphotyrosine-specific phosphoproteomics experiments. Anal Chem. 2011 Oct 15;83(20):7635-44 (view details in PubMed)
Kettenbach AN, Schweppe DK, Faherty BK, Pechenick D, Pletnev AA, Gerber SA. Quantitative phosphoproteomics identifies substrates and functional modules of Aurora and Polo-like kinase activities in mitotic cells. Sci Signal. 2011 Jun 28;4(179):rs5 (view details in PubMed)
Kettenbach AN, Rush J, Gerber SA. Absolute quantification of protein and post-translational modification abundance with stable isotope-labeled synthetic peptides. Nat Protoc. 2011 Feb;6(2):175-86 (view details in PubMed)
Suh EK*, Yang A*, Kettenbach A*, Bamberger C, Michaelis AH, Zhu Z, Elvin JA, Bronson RT, Crum CP, McKeon F. p63 protects the female germ line during meiotic arrest. Nature. 2006 Nov 30;444(7119):624-8 (view details in PubMed)
Full publication list: http://www.ncbi.nlm.nih.gov/sites/myncbi/arminja.kettenbach.1/bibliography/43627887/public/?sort=date&direction=descending.